Retinoschisin

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
RS1
3jd6.jpg
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRS1, RS, XLretinoschisin 1
External IDsOMIM: 300839 MGI: 1336189 HomoloGene: 279 GeneCards: RS1
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for RS1
Genomic location for RS1
BandXp22.13Start18,639,688 bp[1]
End18,672,108 bp[1]
RNA expression pattern
PBB GE RS1 216937 s at fs.png

PBB GE RS1 207363 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000330

NM_011302

RefSeq (protein)

NP_000321

NP_035432

Location (UCSC)Chr X: 18.64 – 18.67 MbChr X: 160.77 – 160.8 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Retinoschisin also known as X-linked juvenile retinoschisis protein is a lectin[5][6] that in humans is encoded by the RS1 gene.[7]

It is a soluble, cell-surface protein that plays an important role in the maintenance of the retina where it is expressed and secreted by retinal bipolar cells and photoreceptors,[8][9] as well as in the pineal gland.[10] Retinoschisin (RS1) is encoded by the gene RS1 located on the X chromosome at p22.1.[7] Young males who have an RS1 mutation are susceptible to retinoschisis, and X-linked eye disease which causes macular degeneration and can lead to a loss of vision.[5][9]

Function[edit]

Retinoschisin is an extracellular protein that plays a crucial role in the cellular organization of the retina: it binds the plasma membranes of various retinal cells tightly to maintain the structure of the retina.[5] In addition to enabling cell-to-cell adhesion, it has been shown that retinoschisin interacts with the sodium/potassium-ATPase (Na/K-ATPase) which resides in the plasma membrane.[10] RS1 also plays a role in the regulation on intracellular MAP kinase signalling.[11]

Structure[edit]

The retinoschisin monomer is 224 amino acids long,[7] including a 23-amino acid signal peptide essential for secretion[5] (this is cleaved off before the protein becomes functional), and a highly conserved sequence motif called the discoidin domain which consists of 157 amino acids,[12] important for the protein's function in cell to cell adhesion.[13] However, its oligomeric structure is a pairing of back-to-back octamers,[8] forming a homo16mer [1]. This structure allows it to adhere to the plasma membrane of retinal cells such as bipolar and photoreceptor cells,[9] joining them together.

Clinical significance[edit]

Pathogenic mutations of this gene are responsible for X-linked retinoschisis an early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision.[14] Female carriers of the RS1 mutation do not show symptoms of X-linked juvenile retinoschisis, except in rare cases where the non-functional protein is expressed due to anomalous X-chromosome inactivation. In young males who carry a gene mutation, the disease presents itself as retinal cavities, splitting of inner retinal layers (also known as foveal schisis),[8][5] and defective synapse activity.[5][12] Retinas that lack mature retinoshisin develop these characteristics in up to 1 in 5,000 males.[11] There are over 200 mutations of RS1 recorded in the Retina International Mutation Database, most of which are not pathogenic.

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102104 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031293 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e f Vijayasarathy C, Ziccardi L, Sieving PA (2012). "Biology of retinoschisin". Advances in Experimental Medicine and Biology. 723: 513–8. doi:10.1007/978-1-4614-0631-0_64. ISBN 978-1-4614-0630-3. PMC 3475158. PMID 22183371.
  6. ^ Wu WW (October 2005). RS1 structure-function relationships: roles in retinal adhesion and X-linked retinoschisis (Ph.D. thesis). The University of British Columbia.
  7. ^ a b c Sauer CG, Gehrig A, Warneke-Wittstock R, Marquardt A, Ewing CC, Gibson A, Lorenz B, Jurklies B, Weber BH (October 1997). "Positional cloning of the gene associated with X-linked juvenile retinoschisis". Nature Genetics. 17 (2): 164–70. doi:10.1038/ng1097-164. PMID 9326935.
  8. ^ a b c Tolun G, Vijayasarathy C, Huang R, Zeng Y, Li Y, Steven AC, Sieving PA, Heymann JB (May 2016). "Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina". Proceedings of the National Academy of Sciences of the United States of America. 113 (19): 5287–92. doi:10.1073/pnas.1519048113. PMC 4868477. PMID 27114531.
  9. ^ a b c Kotova S, Vijayasarathy C, Dimitriadis EK, Ikonomou L, Jaffe H, Sieving PA (August 2010). "Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study". Biochemistry. 49 (33): 7023–32. doi:10.1021/bi1007029. PMC 2929131. PMID 20677810.
  10. ^ a b Plössl K, Royer M, Bernklau S, Tavraz NN, Friedrich T, Wild J, Weber BH, Friedrich U (August 2017). "Retinoschisin is linked to retinal Na/K-ATPase signaling and localization". Molecular Biology of the Cell. 28 (16): 2178–2189. doi:10.1091/mbc.e17-01-0064. PMC 5531734. PMID 28615319.
  11. ^ a b Plössl K, Schmid V, Straub K, Schmid C, Ammon M, Merkl R, Weber BH, Friedrich U (July 2018). "Pathomechanism of mutated and secreted retinoschisin in X-linked juvenile retinoschisis". Experimental Eye Research. 177: 23–34. doi:10.1016/j.exer.2018.07.021. PMID 30040949.
  12. ^ a b Reid SN, Yamashita C, Farber DB (July 2003). "Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells". The Journal of Neuroscience. 23 (14): 6030–40. doi:10.1523/JNEUROSCI.23-14-06030.2003. PMC 6740352. PMID 12853421.
  13. ^ Wu WW, Molday RS (July 2003). "Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis". The Journal of Biological Chemistry. 278 (30): 28139–46. doi:10.1074/jbc.M302464200. PMID 12746437.
  14. ^ Weber BH, Kellner U (2007). "X-Linked Juvenile Retinoschisis". In Tombran-Tink J, Barnstable C (eds.). Retinal Degenerations: Biology, Diagnostics, and Therapeutics. Springer Science & Business Media. pp. 119–135. ISBN 978-1-59745-186-4.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.